Rab32 family proteins regulate autophagosomal components recycling.

In autophagy, autophagosomes deliver the lumenal contents to lysosomes for degradation via autophagosome-lysosome fusion. In contrast, autophagosome outer membrane components were recycled via autophagosomal components recycling (ACR), which is mediated by the recycler complex. The recycler complex, composed of SNX4, SNX5, and SNX17, cooperate with the dynein-dynactin complex to mediate ACR. However, how ACR is regulated remains unknown. Here, we found that Rab32 family proteins localize to autolysosomes and are required for ACR, rather than other autophagosomal or lysosomal Rab proteins. The GTPase activity of Rab32 family proteins, governed by their guanine nucleotide exchange factor and GTPase-activating protein, plays a key role in regulating ACR. This regulation occurs through the control of recycler complex formation, as well as the connection between the recycler-cargo and dynactin complex. Together, our study reveals an unidentified Rab32 family-dependent regulatory mechanism for ACR.

The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion.

Autophagosome-lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome-lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome-lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.

Effects of Chinese Medicine on Pyroptosis in Coronary Heart Disease.

Pyroptosis, an apoptotic pathway for pro-inflammatory cells, has attracted attention from researchers because of its role in the development of cardiac inflammation reactions. Chinese medicine (CM) has been given more and more attention during the pursuit of a treatment for coronary heart disease (CHD). Evidence suggests that myocardial cell pyroptosis affects the progression of CHD. Pyroptosis pathways include the canonical pyroptosis pathway mediated by the caspase-1 inflammasome and the non-canonical pyroptosis pathway induced by cytoplasmic lipopolysaccharide-activated caspase-4/5/11. The frequently studied compounds that regulate pyroptosis in CHD include astragaloside IV (AS-IV), tanshinone IIA, aucubin, cinnamaldehyde (CD), ginsenoside Rb1, paeoniflorin, apigenin, berberine (BBR), ruscogenin (Rus), and total glucosides of paeonia (TGP). The patent drugs of CM that regulate pyroptosis in CHD include the Qishen granule (QSG), the Simiao Yong'an decoction (SMYAD), the Buyang Huanwu decoction (BYHWD), and the Shexiang Baoxin pill (SBP). Therefore, this paper reviews the pathogenesis of pyroptosis, the role of pyroptosis in CHD, and the potential therapeutic roles of CMs and their active ingredients targeting cell pyroptosis in the development of CHD.

ULK phosphorylation of STX17 controls autophagosome maturation via FLNA.

Autophagy is a conserved and tightly regulated intracellular quality control pathway. ULK is a key kinase in autophagy initiation, but whether ULK kinase activity also participates in the late stages of autophagy remains unknown. Here, we found that the autophagosomal SNARE protein, STX17, is phosphorylated by ULK at residue S289, beyond which it localizes specifically to autophagosomes. Inhibition of STX17 phosphorylation prevents such autophagosome localization. FLNA was then identified as a linker between ATG8 family proteins (ATG8s) and STX17 with essential involvement in STX17 recruitment to autophagosomes. Phosphorylation of STX17 S289 promotes its interaction with FLNA, activating its recruitment to autophagosomes and facilitating autophagosome-lysosome fusion. Disease-causative mutations around the ATG8s- and STX17-binding regions of FLNA disrupt its interactions with ATG8s and STX17, inhibiting STX17 recruitment and autophagosome-lysosome fusion. Cumulatively, our study reveals an unexpected role of ULK in autophagosome maturation, uncovers its regulatory mechanism in STX17 recruitment, and highlights a potential association between autophagy and FLNA.

A Case Report of Acupuncture at Neiguan Point (P6) for Paroxysmal Supraventricular Tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) is a common medical emergency, and this case report describes an acupuncture treatment of traditional Chinese medicine terminating PSVT. In this case report, a 67-year-old female patient diagnosed with PSVT had a recurrence in the ward; accompanying symptoms were heart palpitations and shortness of breath. Modified Valsalva maneuver, the first-line treatment, failed to convert paroxysmal supraventricular tachycardia. However, acupuncture at Neiguan point (P6) for about 1 min on her right hand successfully treated the patient. This case indicates that the application of acupuncture in the clinic may serve as an alternative and complementary treatment for PSVT.

[Effect of acupuncture combined with medicine on neuropeptide Y in the patient of hypertension].

OBJECTIVE: To search for a method for increasing therapeutic effect on hypertension and study on the mechanism. METHODS: Seventy-five cases were randomly divided into the treatment group (n=45) treated by acupuncture plus medicine, and the control group (n=30) treated by medicine. Their blood pressure and plasma neuropeptide Y (NPY) before and after treatment were investigated. RESULTS: Blood pressure and NPY content in both the two groups decreased significantly (P < 0.01), and the treatment group in decreasing blood pressure and NPY content was superior to the control group (P < 0.05). CONCLUSION: Acupuncture and medicine have cooperation in treatment of hypertension, which is performed possibly through decreasing NPY.

[Study on stroke syndrome of Chinese medicine and its relationship with blood hypercoagulative status and insulin resistance in diabetic ischemic stroke patients].

OBJECTIVE: To study the relationship of TCM Syndromes, involving Viscera Syndrome and involving Meridian Syndrome, with blood hypercoagulative state and insulin resistance in patients with diabetic ischemic stroke. METHODS: Insulin sensitivity index (ISI) could reflect the insulin resistance, and those reflecting blood hypercoagulative state parameters such as platelet agglutination test (PAgT), fibrinogen (FG), in vitro thrombus length (VTL) and activating partial thrombinogen time (APTT), were used to expound and prove the relationship with the stroke syndrome. RESULTS: The symptom scores, PAgT, VTL, FG levels in patients involved with Viscera Syndromes (including those of Wind Syndrome, Phlegm-Dampness Syndrome, Heat-Fire Syndrome and Yin-deficiency with Yang-excess Syndrome) were significantly higher than those in patients involved with Meridian Syndromes (P < 0.05 or P < 0.01), while the ISI level in the former was lower than that in the latter (P < 0.01). CONCLUSION: There is close relationship between blood hypercoagulative state, insulin resistance and TCM Stroke Syndromes in patients with diabetic ischemic stroke.